This invention is directed to arylsulfonamide compounds. In particular, this invention is directed to arylslulfonamide compounds that are bradykinin antagonists or inverse agonists.
Bradykinin (“BK”) is a kinin which plays an important role in the pathophysiological processes accompanying acute and chronic pain and inflammation. Bradykinin (BK), like other kinins, is an autacoid peptide produced by the catalytic action of kallikrein enzymes on plasma and tissue precursors termed kininogens. The biological actions of BK are mediated by at least two major G-protein-coupled BK receptors termed B1 and B2. It is generally believed that B2 receptors, but not B1 receptors, are expressed in normal tissues and that inflammation, tissue damage or bacterial infection can rapidly induce B1 receptor expression. This makes the B1 receptor a particularly attractive drug target. The putative role of kinins, and specifically BK, in the management of pain and inflammation has provided the impetus for developing potent and selective BK antagonists. In recent years, this effort has been heightened with the expectation that useful therapeutic agents with analgesic and anti-inflammatory properties would provide relief from maladies mediated through a BK receptor pathway (see e.g., M. G. Bock and J. Longmore, Current Opinion in Chem. Biol., 4:401-406(2000)). Accordingly, there is a need for novel compounds that are effective in blocking or reversing activation of bradykinin receptors. Such compounds would be useful in the management of pain and inflammation, as well as in the treatment or prevention of diseases and disorders mediated by bradykinin; further, such compounds are also useful as research tools (in vivo and in vitro).
Chemical Abstracts No. 108:131304 (1988; German Patent Application DE3544409) discloses compounds of the formula:
as inhibitors of cyclooxygenase and lipoxygenase. The compound N-[4-[[(2-benzoylphenyl)amino]-sulfonyl]phenyl]acetamide is specifically disclosed.
U.S. Pat. No. 6,403,607 discloses compounds of the formula:
useful as treatment for peptic ulcers.
WO 95/33461 discloses anti-inflammatory compounds of the formula:

Du et al., Chemistry & Biology, 2000, 7(9):733-742 discloses the compound

Kloetzel et al., J. Med. Pharm. Chem., 1959, 1:197-211 discloses the compound

In Proc. Indian Acad. Sci. Sect. A, 15, 1942, p. 432-end, there is disclosed the compound

The compound N-[4-[[(2-benzoyl-4-chlorophenyl)amino]sulfonyl]phenyl]acetamide is registered with Chemical Abstracts Services as CAS RN 392305-40-7.
PCT Published Application WO03/099773 discloses CCR9 inhibitors of the formula:
